Positron emission tomography (PET) is a diagnostic imaging technique for measuring the metabolic activity of cells in the human body. PET can show images of blood flow, glucose metabolism in the brain, or rapid changes in activity in various areas of the body. It can be used to show changes in physiology before any change in gross anatomy has occurred. PET has been used in diagnosing diseases such as cancer, heart disease, Alzheimer's disease, Parkinson's disease, and schizophrenia.
PET uses chemical compounds that are labeled with radioactive atoms that decay by emitting positrons. The most commonly used PET radioisotopes are 11C, 13N, 15O, and 18F. Typically, the labeled compound is a natural substrate, substrate analog, or drug that is labeled with a radioisotope without altering the compound's chemical or biological properties. After injection into the tissue, the radiolabeled compound should follow the normal metabolic pathway of its unlabeled counterpart. The labeled compound emits positrons as it moves through the tissue. Collisions between the positrons and electrons that are present in the tissue emit gamma rays that are detectable by a PET scanner.
3,4-dihydroxyphenyl-L-alanine (L-Dopa) is the precursor for the neurotransmitter dopamine. L-Dopa is transported to the brain and is picked up by the nerve cells that produce dopamine. Once there, L-Dopa is converted into dopamine for the nerve cells to use as a neurotransmitter.
18F-labeled PET tracers have been used clinically in the study and diagnosis of brain abnormalities. In particular, 3,4-dihydroxy-6-[18F]fluoro-L-phenyl alanine (18F-Dopa) is a radiolabeled analog of L-Dopa that has been used in neurology to study metabolism, neurotransmission, and cell processes. 18F-Dopa is a PET tracer that is used to analyze the presynaptic domaine function in animals and humans. Clinical diagnosis of Parkinson's disease and other biological disorders are easily determined via synaptic uptake of 18F-Dopa into various regions of the brain. 3,4-dihydroxy-6-fluoro-L-phenyl alanine (F-Dopa) is an analytical standard that is useful in the evaluation of 18F-Dopa compounds. Clinical use of 18F-Dopa has steadily increased resulting in a need to provide quicker and more efficient methods of its production.
Typical methods of preparing F-Dopa and 18F-Dopa result in racemic (d,l) mixtures that often require additional steps to isolate the L-enantiomer. Other methods avoid the need to resolve the enantiomers by starting with L-Dopa or L-3,4-dimethoxyphenyl alanine. Although these methods do not require additional steps to isolate the desired L-enantiomer, they have disadvantages that affect yield and efficiency.
Thus, there still exists a need for a method of preparing F-Dopa and 18F-Dopa in which the desired enantiomer can selectively be produced in high yield with high optical purity in a short number of synthetic steps without the need for extensive resolution.